The impact of the quantitative assessment procedure for coronary artery bypass graft evaluations using high-resolution near-infrared fluorescence angiography.

PURPOSE: Near-infrared angiography (NIR) is used for on-site graft assessment during coronary artery bypass grafting. This study evaluated the results of a quantitative NIR assessment using a new high-resolution NIR device (h-NIR) for graft assessment. METHODS: Forty-three patients were enrolled in our study. Internal thoracic artery (ITA) grafts anastomosed to the left anterior descending artery and examined intraoperatively using h-NIR were included. The ITA grafts were divided into 2 groups for a comparative analysis: patent grafts (P group; n = 37) and failed grafts (F group; n = 6). The graft flow was evaluated by a "quantitative NIR assessment", and the fluorescence luminance intensity (FLI) was measured. Direct observation of the graft and anastomosis with h-NIR was also performed. RESULTS: The FLI was higher in the P group than in the F group. The receiver operating characteristic analysis revealed the following cut-off values for FLIs depending on imaging duration: 21.1% at 1 s, 35.5% at 2 s, 58.4% at 3 s, and 83.3% at 4 s. The sensitivity and specificity for detecting graft failure were 83.3% and 69.8-80.6%, respectively. Furthermore, h-NIR was also able to visualize arterial dissection in ITA grafts. CONCLUSIONS: A quantitative NIR assessment with an h-NIR device can improve the detectability of anastomotic stenosis, and h-NIR successfully detected arterial dissection of grafts.

Evaluation of graft anastomosis using time-intensity curves and quantitative near-infrared fluorescence angiography during peripheral arterial bypass grafting.

Near-infrared fluorescence angiography (NIR) visualizes blood perfusion using the fluorescence property of indocyanine green (ICG). This study aimed to retrospectively determine the usefulness of a quantitative analysis using NIR to predict the patency of peripheral arterial bypass grafts by measuring their fluorescence luminance intensities (FLIs).Thirteen grafts in 11 patients who underwent peripheral arterial bypass grafting were divided into a patent graft group (n = 7) and a failed graft group (n = 6). The changes in the FLIs of ICG opacification through the graft and distal host artery were retrospectively analyzed using stored NIR data. The time-intensity curves (TICs) of ICG opacification through the graft (Qgraft) and distal host artery (Qdistal) were measured. Two parameters, Δ(Qgraft - Qdistal) and integral(Qgraft - Qdistal), were also analyzed.Although not significant, decreases in Qgraft were observed in the failed graft groups. The Qdistal of the failed graft group was significantly attenuated as compared with that of the patent graft group. Δ(Qgraft - Qdistal) increased only in the failed graft group, which indicates widening of the gap in FLI. Integral(Qgraft - Qdistal) was higher in the failed graft group, as it reflects the accumulation of ICG opacification.The TICs were influenced by anastomotic stenosis in the distal site of the host arteries. Our results indicate that the comparison of Δ(Qgraft - Qdistal) and integral (Qgraft - Qdistal) quantitatively analyzed using NIR can potentially predict anastomotic stenosis.

Quantitative assessment technique of HyperEye medical system angiography for coronary artery bypass grafting.

PURPOSE: The HyperEye Medical System (HEMS) uses indocyanine green (ICG) to visualize blood vessels in coronary artery bypass grafting (CABG). We performed quantitative HEMS assessment to detect grafts at risk of occlusion. METHODS: We assessed the HEMS angiograms of 177 grafts from 69 patients who underwent CABG and compared the results with those of fluoroscopic coronary angiography, by measuring the increasing rate of ICG intensity, average acceleration value, and time to peak luminance intensity. RESULTS: Grafts in the patent and failed groups showed significant differences in their increasing rate of intensity and average acceleration value. The average accelerations value of ICG intensity of internal thoracic artery (ITA) and saphenous vein (SV) grafts were 112.3 and 144.9 intensity/s2 in the patent group, and 71.0 and 91.8 intensity/s2 in the failed group. The time to peak luminance intensity was 1.7 and 1.4 s in the patent group and 2.3 and 1.9 s in the failed group; these values were not significantly different. CONCLUSION: Significant reductions in the ICG intensity rate and average acceleration value can occur in failed grafts. Therefore, quantifiable changes in ICG intensity may help detect minute changes in blood flow.

Multiple organ embolization with vegetation on an elephant trunk graft.

We encountered a rare case of infection in a vascular graft created using the elephant trunk technique. A 65-year-old woman who underwent total arch replacement with the elephant trunk technique was re-admitted with fever. She developed embolization of multiple organs from vegetation attached to the elephant trunk graft which was elucidated by transesophageal echocardiography. Surgery for ruptured jejunal artery aneurysm was performed, and the graft infection healed after long-term antibiotic therapy with the prosthesis left in situ. Graft infection may generate vegetations on an elephant trunk graft. Transesophageal echocardiography is a helpful tool for accurate diagnosis.

Influence of vessel stenosis on indocyanine green fluorescence intensity assessed by near-infrared fluorescence angiography.

PURPOSE: Although useful for visualizing blood flow during revascularization surgery, the permeability of near-infrared fluorescence (NIR) angiography using indocyanine green (ICG) does not allow for vessel stenosis visualization. We hypothesized that changes in ICG fluorescence intensity reflect vessel stenosis, and evaluated the influence of stenosis on blood flow by ex vivo experimentation. METHODS: The vessel stenosis model comprised a silicon tube, a graft occluder, and artificial blood. During near-infrared angiography, the fluorescense intensity was calculated during pre- and post-stenosis of an artificial circuit, using a NIR angiography. We measured the maximum fluorescence intensity and the time to maximum fluorescence intensity. RESULTS: Severe stenosis (≥75%) attenuated the increase in ICG fluorescence intensity in the tube significantly, pre- and post-stenosis. The time to maximum fluorescence intensity did not differ between sites pre- and post-stenosis, irrespective of stenosis severity. CONCLUSION: Stenosis affected the ICG fluorescence intensity through the vessel. Thus, quantitative analysis using NIR angiography may detect severe vessel stenosis (≥75%), and the extinction curve of indocyanine fluorescence intensity may support the evaluation of blood flow. The absence of differences in the time to maximum fluorescence intensity for degrees of stenosis might suggest a limitation of previous conventional qualitative assessments.

Maximal blood flow acceleration analysis in the early diastolic phase for aortocoronary artery bypass grafts: a new transit-time flow measurement predictor of graft failure following coronary artery bypass grafting.

PURPOSE: Maximal graft flow acceleration (max df/dt) determined using transit-time flowmetry (TTFM) in the diastolic phase was assessed as a potential predictor of graft failure for aortocoronary artery (AC) bypass grafts in coronary artery bypass patients. METHODS: Max df/dt was retrospectively measured in 114 aortocoronary artery bypass grafts. TTFM data were fitted to a 9-polynomial curve, which was derived from the first-derivative curve, to measure max df/dt (9-polynomial max df/dt). Abnormal TTFM was defined as a mean flow of <15 ml/min, a pulsatility index of >5 or a diastolic filling ratio of <50 %. Postoperative assessments were routinely performed by coronary artery angiography (CAG) at 1 year after surgery. RESULTS: Using TTFM, 68 grafts were normal, 4 of which were failing on CAG, and 46 grafts were abnormal, 21 of which were failing on CAG. 9-polynomial max df/dt was significantly lower in abnormal TTFM/failing by the CAG group compared with abnormal TTFM/patent by the CAG group (1.08 ± 0.89 vs. 2.05 ± 1.51 ml/s(2), respectively; P < 0.01, Mann-Whitney U test, Holm adjustment). CONCLUSIONS: TTFM 9-polynomial max df/dt in the early diastolic phase may be a promising predictor of future graft failure for AC bypass grafts, particularly in abnormal TTFM grafts.

[Operative Results of Total Arch Replacement with Arch First Technique using a Trifurcated Graft].

In aortic arch surgery, we reconstruct branches before opening the arch to avoid cerebral embolism of the debris derived from the aortic wall. We made a trifurcated graft for branch reconstruction using 10 mm and 8 mm polyester grafts. Cardiopulmonary bypass started under right axillary perfusion and venous drainage through the right atrium. While cooling, the left subclavian artery was clamped and anastomosed to the end of the trifurcated graft. Then the ascending aorta was cross-clamped and cardioplegic solution was infused. At 25 degrees centigrade of the tympanic temperature, the left carotid artery is clamped and anastomosed to the branch of the trifurcated graft with or without perfusion into the left carotid artery. Subsequently the brachiocephalic artery was reconstructed in the same manner. After antegrade cerebral perfusion was established through the trifurcated graft via right axillary perfusion, distal anastomosis of the aortic arch was done with the open distal technique. Graft-graft anastomosis was followed to reperfuse the lower half of the body. Finally proximal anastomosis was performed to complete total arch replacement. Forty-four patients underwent total arch replacement in this technique. In-hospital mortality was 4.5%. Cerebral infarction occurred in 4.5% of the patients probably due to embolization of the debris derived from the branches of the aortic arch.

Maximal blood flow acceleration analysis in the early diastolic phase for in situ internal thoracic artery bypass grafts: a new transit-time flow measurement predictor of graft failure following coronary artery bypass grafting.

OBJECTIVES: Maximal graft flow acceleration (max df/dt) determined by transit-time flowmetry (TTFM) in the diastolic phase was assessed as a possible predictor of graft failure in coronary artery bypass patients. METHODS: Max df/dt was retrospectively measured in 57 in situ left internal thoracic artery grafts. TTFM data were fitted to a 5-polynomial curve, which was derived from the first-derivative curve to measure max df/dt (5-polymial max df/dt). Abnormal TTFM was defined as a mean flow of <15 ml/min, pulsatility index of >5 or diastolic filling ratio of <50%. Postoperative coronary angiography (CAG) or multidetector computed tomography (MDCT) was performed within 1 year after surgery. The grafts were classified into four groups: Normal TTFM/Patent MDCT/CAG (N/P), Normal TTFM/Failing MDCT/CAG (N/F), Abnormal TTFM/Patent MDCT/CAG (Ab-N/P) and Abnormal TTFM/Failing MDCT/CAG graft (Ab-N/F). RESULTS: By TTFM, 34 grafts were normal, 5 of which were occluded on CAG, and 23 grafts were abnormal, six of which were occluded on CAG. There were significant differences in 5-polynomial max df/dt between each group pair (P < 0.05, Mann-Whitney U-test) except for the N/F:Ab-N/P group pair; especially, 5-polynomial max df/dt was significantly lower in the Ab-N/F group compared with the other groups (Ab-N/F: 0.89 ± 0.41 vs N/P: 4.74 ± 3.18, N/F: 2.23 ± 0.65, Ab-N/P: 2.70 ± 1.31 ml/s(2), P < 0.01, Mann-Whitney U-test). The sensitivity and specificity of 5-polynomial max df/dt were, respectively, 72.7 and 80.4% (cut-off value, 1.918 ml/s(2)) for all grafts and 100 and 88.2% (cut-off value, 1.273 ml/s(2)) for abnormal TTFM grafts. CONCLUSIONS: The TTFM 5-polymial max df/dt value in the early diastolic phase may be a promising predictor of future graft failure.

Efficacy of intraoperative HyperEye Medical System angiography for coronary artery bypass grafting.

PURPOSE: When performing coronary artery bypass grafting, anastomotic insufficiency needs to be detected during surgery. We developed a novel indocyanine green angiography system, the HyperEye Medical System (HEMS), which enables color imaging of the bypass flow. This article described the accuracy of HEMS angiography for predicting graft patency. METHODS: A total of 144 grafts in 40 coronary artery bypass grafting patients were assessed by HEMS angiography, a transit time flowmeter (TTF) during surgery and fluoroscopic angiography 1 year after the operation. RESULTS: HEMS angiography showed normal flow in 133 grafts, but abnormal flow in 11. Fluoroscopic angiography showed that 130 of the 133 "normal" grafts were patent (negative predictive value: 97.7%) and that nine of the 11 "abnormal" grafts were occluded (positive predictive value: 81.8%). As a result, 134 grafts were assessed as normal and 10 as abnormal by TTF. Fluoroscopic angiography showed that 124 of these 134 grafts were patent (negative predictive value: 92.5%), whereas two of the 10 grafts were occluded (positive predictive value: 20.0%). For the 127 grafts with compatible results by the HEMS and TTF assessments, the positive and negative predictive values were 100 and 97.6%, respectively. CONCLUSION: HEMS angiography of a bypass graft may provide an accurate prediction of the graft patency after surgery.

Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.

BACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. METHODS AND RESULTS: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. CONCLUSION: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.

New device for intraoperative graft assessment: HyperEye charge-coupled device camera system.

PURPOSE: Our institution developed a new color chargecoupled device (CCD) camera system (HyperEye system) for intraoperative indocyanine green (ICG) angiography. The device consists of a combination of custommade optical filters and an ultra-high-sensitive CCD image sensor with non-Bayer color filter array (i.e., HyperEye technology), which can detect simultaneously color and near-infrared (NIR) rays from 380 to 1200 nm. Here, we demonstrate intraoperative graft assessment using the HyperEye system. METHODS: We investigated the intraoperative graft patency using both the HyperEye system and transittime flowmetry (TFM) in 51 patients between April 2007 and April 2009 while ICG dye was injected through a central venous catheter. Each patient signed a consent form before the surgery. RESULTS: We obtained intraoperative graft flows and images in 189 anastomoses of 153 grafts. Both the HyperEye system and TFM indicated the patency of the grafts in 129 grafts. Both the HyperEye system and TFM detected the abnormality of the graft in seven grafts. For the competitive flows, the HyperEye system captured to-and-fro flow fluorescence and TFM detected the retrograde waveform in 16 grafts. On the other hand, although TFM indicated the patency of the graft, the HyperEye system suspected nonoccluded graft failure in seven grafts. In contrast, although TFM detected a mean flow of <10 ml/min, the HyperEye system captured the patent perfusion fluorescence in four grafts. CONCLUSION: The HyperEye system can visualize any structural and functional failures. Our findings suggest that this device could become a useful tool for intraoperative graft assessment.

Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model.

Our recent studies have indicated that acetylcholine (ACh) protects cardiomyocytes from prolonged hypoxia through activation of the PI3K/Akt/HIF-1alpha/VEGF pathway and that cardiomyocyte-derived VEGF promotes angiogenesis in a paracrine fashion. These results suggest that a cholinergic system plays a role in modulating angiogenesis. Therefore, we assessed the hypothesis that the cholinergic modulator donepezil, an acetylcholinesterase inhibitor utilized in Alzheimer's disease, exhibits beneficial effects, especially on the acceleration of angiogenesis. We evaluated the effects of donepezil on angiogenic properties in vitro and in vivo, using an ischemic hindlimb model of alpha7 nicotinic receptor-deleted mice (alpha7 KO) and wild-type mice (WT). Donepezil activated angiogenic signals, i.e., HIF-1alpha and VEGF expression, and accelerated tube formation in human umbilical vein endothelial cells (HUVECs). ACh and nicotine upregulated signal transduction with acceleration of tube formation, suggesting that donepezil promotes a common angiogenesis pathway. Moreover, donepezil-treated WT exhibited rich capillaries with enhanced VEGF and PCNA endothelial expression, recovery from impaired tissue perfusion, prevention of ischemia-induced muscular atrophy with sustained surface skin temperature in the limb, and inhibition of apoptosis independent of the alpha7 receptor. Donepezil exerted comparably more effects in alpha7 KO in terms of angiogenesis, tissue perfusion, biochemical markers, and surface skin temperature. Donepezil concomitantly elevated VEGF expression in intracardiac endothelial cells of WT and alpha7 KO and further increased choline acetyltransferase (ChAT) protein expression, which is critical for ACh synthesis in endothelial cells. The present study concludes that donepezil can act as a therapeutic tool to accelerate angiogenesis in cardiovascular disease patients.

Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice.

BACKGROUND: We previously reported that chronic vagal nerve stimulation markedly improved long-term survival after chronic heart failure (CHF) in rats through cardioprotective effects of acetylcholine, independent of the heart rate-slowing mechanism. However, such an approach is invasive and its safety is unknown in clinical settings. To develop an alternative therapy with a clinically available drug, we examined the chronic effect of oral donepezil, an acetylcholinesterase inhibitor against Alzheimer's disease, on cardiac remodeling and survival with a murine model of volume-overloaded CHF. METHODS AND RESULTS: Four weeks after surgery of aortocaval shunt, CHF mice were randomized into untreated and donepezil-treated groups. Donepezil was orally given at a dosage of 5 mgxkg(-1)xday(-1). After 4 weeks of treatment, we evaluated in situ left ventricular (LV) pressure, ex vivo LV pressure-volume relationships, and LV expression of brain natriuretic peptides (BNP). We also observed survival for 50 days. When compared with the untreated group, the donepezil-treated group had significantly low LV end-diastolic pressure, high LV contractility, and low LV expression of BNP. Donepezil significantly reduced the heart weight and markedly improved the survival rate during the 50-day treatment period (54% versus 81%, P < .05). CONCLUSIONS: Oral donepezil improves survival of CHF mice through prevention of pumping failure and cardiac remodeling.

Preliminary experience for the evaluation of the intraoperative graft patency with real color charge-coupled device camera system: an advanced device for simultaneous capturing of color and near-infrared images during coronary artery bypass graft.

We developed a new color charge-coupled device (CCD) camera for the intraoperative indocyanine green (ICG) angiography. This device consists of a combination of custom-made optical filters and an ultra-high sensitive CCD image sensor, which can detect simultaneously color and near-infrared (NIR) rays from 380 to 1200 nm. We showed a comparison between our system and other devices for the preliminary experience. We routinely performed both transit-time flowmetry (TFM) and color images for intraoperative assessment, thallium-scintigraphy for the early postoperative assessment, and then angiography after 1-year surgery. We also obtained intraoperative graft flows and images in 116 grafts. Although TFM indicated a graft patency, the CCD camera suspected perfusion failures in four grafts. Also the analysis of the ICG fluorescence intensity showed the significant hypoperfusion at the perfusion territory distal to the anastomosis (graft vs. perfusion territory; 230+/-26 vs. 156+/-13 a.u, P=0.02). When the CCD camera suspected a graft failure, CCD camera and angiography showed a comparable graft failure. The unique device that visualized ICG-enhanced structures against a background of natural myocardial color improved the visibility of abnormality in flow and perfusion. Our findings show that this device may become a standard intraoperative graft and perfusion assessment tool in coronary artery bypass graft (CABG).

Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac effect.

BACKGROUND: In spite of recent advances in coronary interventional therapy, reperfusion injury is still considered to be a major problem in patients undergoing surgical procedures, such as bypass grafting. Here we demonstrate a novel therapeutic strategy against ischemia-reperfusion injury: vagally mediated prevention of reperfusion-induced opening of mitochondrial permeability transition pore. METHODS: We investigated the effects of efferent vagal stimulation on myocardial reperfusion injury with ex vivo and in vitro rat models. In the ex vivo model the hearts were perfused with intact vagal innervation, which allowed us to study the effects of the vagal nerve on the heart without other systemic effects. RESULTS: Compared with sham stimulation, vagal stimulation exerted a marked anti-infarct effect irrespective of the heart rate (34% +/- 6% vs 85% +/- 9% at a heart rate of 300 beats/min, 37% +/- 4% vs 43% +/- 5% at a heart rate of 250 beats/min, and 39% +/- 4% vs 88% +/- 7% at a heart rate of 350 beats/min) after a 30-minute period of global ischemia, activated cell-survival Akt cascade, prevented downregulation of the antiapoptotic protein Bcl-2, and suppressed cytochrome-c release and caspase-3 activation. Furthermore, vagal stimulation-treated hearts exhibited a significant improvement in left ventricular developed pressure (78 +/- 5 vs 45 +/- 8 mm Hg) and a significant attenuation in an incremental change in left ventricular end-diastolic pressure during reperfusion. These beneficial effects of vagal stimulation were abolished by a permeability transition pore opener, atractyloside. In the in vitro study with primary-cultured cardiomyocytes, acetylcholine prevented a reoxygenation-induced collapse in mitochondrial transmembrane potential through inhibition of permeability transition pore opening. CONCLUSION: Vagal stimulation would be a potential adjuvant therapy for the rescue of ischemic myocardium from reperfusion injury, and the protective effects are independent of its bradycardiac effects.

Shaggy aorta syndrome after acute arterial macroembolism: report of a case.

We report the case of a patient who underwent treatment for a macroembolism in the right lower leg, which led to shaggy aorta syndrome. Anticoagulant therapy for the macroembolism and intra-aortic catheterization exacerbated the patient's renal function and triggered another massive microembolization of the visceral arteries, with a fatal outcome. To minimize the incremental complications inherent to this syndrome, awareness and prompt diagnosis with enhanced computed tomography or intravenous digital subtraction aortography are essential. Axillo-bifemoral bypass with bilateral external iliac artery ligations, performed with optimal timing, could save patients with shaggy aorta syndrome.